title: Exome sequencing identifies novel compound heterozygous mutations in SPG11 that cause autosomal recessive hereditary spastic paraplegia.
abstract: Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized by progressive weakness and spasticity of the lower limbs, in complicated forms, with additional neurological signs. To identify the genotype and characterize the phenotype in a Chinese HSP family, ten subjects from the family were examined through detailed clinical evaluations, auxiliary examinations and genetic tests. Using a combined approach of whole-exome sequencing and candidate mutation validation, we identified novel compound heterozygous mutations in the SPG11 gene of the patients as follows: a nonsense mutation c.6856C>T (p.R2286X) in exon 38 and a deletion mutation c.2863delG (p.Glu955Lysfs*8) in exon 16. Both mutations co-segregated with the phenotype in this family and were absent in 100 normal Chinese individuals. Our finding suggests that the novel compound heterozygous mutations in SPG11 are associated with HSP. We were able to assess the future risk of HSP in healthy younger family members using genetic detection, and provide prenatal diagnoses for the family members. Furthermore, to some extent, this new finding enriches the information on SPG11 and may provide a new basis for the genetic diagnosis of HSP.
authors.affiliation: Department of Neurology, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing 100853, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Qing-Yan
authors.initials: QY
authors.lastname: Zhu
authors.forename: Jia-Tang
authors.initials: JT
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Chen
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Guan
authors.forename: Xu-Sheng
authors.initials: XS
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Yu
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D003337:Corpus Callosum / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D011506:Proteins; C520412:SPG11 protein, human
keywords: AD; AR; Autosomal recessive; CSF; EEG; Genetics; HSP; Hereditary spastic paraplegia; MMSE; MRI; Mini-Mental State Examination; NGS; SPG; SPG11; TCC; Thin corpus callosum; Whole-exome sequencing; autosomal dominant; autosomal recessive; cerebrospinal fluid; electroencephalogram; magnetic resonance imaging; next-generation sequencing; spastic paraplegia gene; thin corpus callosum